Chemical methods have been developed recently for the synthesis of large combinatorial libraries of peptides and oligonucleotides that are later screened against a specific receptor or enzyme to determine the key molecular recognition elements of the compound for that receptor or enzyme. Unfortunately, peptides and oligonucleotides tend to have limited oral activities due to their large size and rapid clearing times resulting in part from their susceptibility to enzymatic degradation. Therefore, such materials tend to have limited utility as therapeutic agents. In such cases it would be beneficial to have access to small molecules which have inherently greater oral activities and are resistant to enzymatic attack.
Virtually any biologically active organic compound can be accessed by chemical synthesis; however, such organic compounds are still synthesized and evaluated one at a time in many cases. This limitation is especially severe when the magnitude of the challenge of finding a biologically active compound is considered. A recent report concluded that, on average, over 10,000 compounds must be screened before one biologically active compound is discovered. Science, Vol. 259 p. 1564 (Mar. 12, 1993). This limitation could be overcome by developing a methodology for the combinatorial synthesis of large numbers of derivatives of therapeutically important classes of organic compounds. Screening these compounds against key receptors or enzymes would then greatly accelerate the acquisition of useful structure versus recognition data and would revolutionize the search for potent new therapeutic agents.
From the above it is seen that improved methods, compositions, and devices for synthesis of therapeutically useful compounds are desired.